| RRC ID |
42254
|
| 著者 |
Onuma E, Sato K, Saito H, Tsunenari T, Ishii K, Esaki K, Yabuta N, Wakahara Y, Yamada-Okabe H, Ogata E.
|
| タイトル |
Generation of a humanized monoclonal antibody against human parathyroid hormone-related protein and its efficacy against humoral hypercalcemia of malignancy.
|
| ジャーナル |
Anticancer Res
|
| Abstract |
A humanized monoclonal antibody against parathyroid hormone-related protein (PTHrP) was generated from the mouse monoclonal antibody raised against the peptide corresponding to the N-terminal 34 amino acids of the human PTHrP [(PTHrP(1-34)]. The humanized antibody interacted with the PTHrP(1-34) with a kD value of 1.90 x 10(-10) M, and the epitope resides between the amino acids 20 and 30 of the PTHrP. PTHrP(1-34) significantly increased the intracellular cAMP levels in the rat osteosarcoma cells that expressed PTHR1, and the 5 microg/mL or higher concentrations of the humanized antibody almost completely blocked the PTHrP-induced cAMP production even in the presence of 2 microg/mL PTHrP(1-34), demonstrating its ability to fully neutralize PTHrP function. There was no significant difference in the potency of the mouse, chimera, or the humanized antibodies to suppress the PTHrP-induced increase in the intracellular cAMP in ROS cells. Furthermore, at the same doses, the administration of the chimera or the humanized antibody was equally effective in reducing the blood ionized calcium levels of hypercalcemic mice bearing the PAN-7-JCK human pancreatic cancer xenograft or the LC-6-JCK human lung cancer xenograft that secreted PTHrP. Thus, humanized anti-PTHrP may be useful for the treatment of the humoral hypercalcemia of malignancy in humans.
|
| 巻・号 |
24(5A)
|
| ページ |
2665-73
|
| 公開日 |
2004-1-1
|
| PMID |
15517871
|
| MeSH |
Amino Acid Sequence
Animals
Antibodies, Monoclonal / biosynthesis
Antibodies, Monoclonal / genetics
Antibodies, Monoclonal / immunology*
Antibodies, Monoclonal / pharmacology*
Cell Line, Tumor
Humans
Hypercalcemia / blood
Hypercalcemia / etiology
Hypercalcemia / therapy*
Immunoglobulin Heavy Chains / genetics
Immunoglobulin Light Chains / genetics
Lung Neoplasms / blood
Lung Neoplasms / complications
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Molecular Sequence Data
Pancreatic Neoplasms / blood
Pancreatic Neoplasms / complications
Parathyroid Hormone-Related Protein / antagonists & inhibitors*
Parathyroid Hormone-Related Protein / immunology*
Peptide Fragments / immunology*
Rats
Rats, Inbred F344
Rats, Nude
Recombinant Fusion Proteins / biosynthesis
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / immunology
Recombinant Fusion Proteins / pharmacology
Xenograft Model Antitumor Assays
|
| IF |
1.994
|
| 引用数 |
27
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
|
